Liposomes are membrane-like vesicles consisting of series of concentric lipid bilayers alternating with hydrophilic compartments. They can be made from a variety of natural and synthetic lipids such as natural and synthetic phosphoglycerolipids, sphingolipids, and digalactosylglycerolipids. One of the main uses for liposomes has been as carriers for different kinds of pharmaceutically active components, in order to improve drug delivery and to minimise side-effects of some treatments. The pharmaceutically active components can be incorporated into liposomes either by encapsulation in hydrophilic compartments of the liposome (when the active component is water-soluble), or by encapsulation into the lipid bilayers, when the active component is lipophilic.
One of the major problems associated with pharmaceutical liposomal formulations is the long-term stability. Aqueous liposome dispersions have a limited stability due to aggregation, loss of the encapsulated active component to the external phase, chemical degradation of the active component or the lipid material, etc.
These problems can to a large extent be overcome if a solid composition is used. Such a solid composition can comprise a liposome powder, i.e. a dried liposome dispersion or a proliposome powder.
The process of drying liposome dispersions has the associated risk of damage to the liposome membranes. In order to minimise this risk it is necessary to dry the liposomes in the presence of protective sugars, as described for example in WO 86/01103.
U.S. Pat. No. 4,906,476 discloses liposome formulations for the delivery of steroids by inhalation. The possibility of delivering dried liposomes as a powder aerosol using a suitable device is disclosed. Delivery by spraying from a self-contained atomiser using a propellant solvent with suspended dried liposomes in a powder, dnd by spraying dried particles into the lungs with a propellant, is also disclosed.
Liposomes as such are not present in proliposome powders, but are formed when the powder is hydrated above the phase transition temperature of the lipids. Compared with dried liposomes, proliposome powders therefore have the advantage that the risk of damage to the liposome membranes on dehydration is eliminated.
Proliposome powders have been described previously.
For example, U.S. Pat. No. 4,311,712 discloses a freeze-dried potential liposome mixture obtained by dissolving a liposome-forming amphipathic lipid and a lipid-soluble or lipid-bound biologically active compound in an organic solvent which remains solid during the freeze-drying process, and freeze-drying the solution. The potential liposome mixture may be stored and made up into an aqueous liposome preparation when desired. The biologically active compound may be any compound having a property of biological interest.
WO 90/00389 discloses a freeze-dried potential liposome mixture having an amphipathic lipid and a cyclosporin or derivative thereof, for use in possible liposome delivery of cyclosporin into cells. The freeze-dried mixture is reconstituted in aqueous medium to yield liposomes which encapsulate substantially all of the cyclosporin present in the freeze-dried mixture.
WO 92/11842 discloses a preliposomal powder which forms a suspension of liposomes containing a polyene drug such as nystatin when reconstituted with water or saline solution.
All of the above patents and applications concerning proliposome compositions are concerned with compositions which are to be hydrated prior to administration.
EP 309464 describes proliposome powder compositions which may be inhaled. The powder compositions comprise solid particles in which a biologically active component is in particulate dispersion in a lipid.